To date, hiPSC model systems have not only confirmed previous findings about the pathogenesis of neurodevelopmental disorders, but provided further detail and nuances, and shed light on the mechanisms underlying the associated manifestations. Altered synaptic connectivity and density, excitation inhibition imbalance, and altered neuronal activity had all been proposed as having a role as a result of postmortem, neuroimaging and genetic studies, and hiPSCs have been able to establish a level of causality for these mechanisms, because they provide the means for experimentally manipulating the system. Promisingly, these causal relationships have been used to successfully reverse observed abnormal phenotypes. Furthermore, hiPSCs have demonstrated when these phenotypic alterations first occur, the events leading up to their first occurrence, and how they progress, whereas postmortem studies were only able to examine a single time point, often remote from the genesis of the disorder. In some cases the phenotypic observations, such as neuron size and detailed spine morphology, made in patient-derived neurons are entirely novel and were previously unobservable. Still, we think there is much left to be discovered especially in using hiPSCs
